Projects per year
Abstract
Despite advances in combination therapies for cancer treatment, most strategies rely on modular-additive designs that lack dynamic molecular cues to achieve intrinsic synergy. Herein, a mitochondrial-targeted nanoplatform is introduced that orchestrates photodynamic therapy (PDT), mild photothermal therapy (mPTT), and enzyme dynamic therapy (EDT) into a self-amplifying cascade network through gasotransmitter (H 2S)-driven metabolic reprogramming. It is constructed from an Au 2Pt core with a surface functionalized mesoporous silica shell loaded with photosensitizers, encapsulated within a tumor cell membrane (Au 2Pt@4sMSN/PS-TPP@CM). Upon GSH exposure, nanomotors produce H 2S to boost diffusive motion, while TPP targeting directs this motility toward mitochondria, enabling efficient mitochondrial accumulation (internalization of >100 nm nanoparticles). Subsequently, mitochondrial targeted H 2S releasing-mediated suppression of oxidative phosphorylation amplifies PDT efficacy; HSP70 downregulation enables mPTT; and hyperactive glycolytic metabolism fuels EDT. Furthermore, these enhanced modalities also interconnect in a positive feedback loop: mPTT-derived hyperthermia accelerates EDT-catalyzed oxygen generation for PDT, while mitochondria-localized PDT further inhibits HSP70 to boost mPTT. Ultimately, these interconnected molecular cues establish an H 2S-driven, self-reinforcing therapeutic loop that enables effective eradication of hepatocellular carcinoma. Collectively, this study identifies mitochondria as the biological initiator and signal integrator for multimodal therapy, delivering a distinctive paradigm to overcome the limitations of conventional combination therapies.
| Original language | English |
|---|---|
| Journal | Advanced Materials |
| DOIs | |
| Publication status | Published - Dec 2025 |
| MoE publication type | A1 Journal article-refereed |
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Åbo Akademi Functional Printing Center
Toivakka, M. (PI), Rosenholm, J. (PI), Anttu, N. (PI), Bobacka, J. (PI), Huynh, T. P. (PI), Peltonen, J. (PI), Wang, X. (PI), Wilen, C.-E. (PI), Xu, C. (PI), Zhang, H. (PI) & Österbacka, R. (PI)
Faculty of Science and EngineeringFacility/equipment: Facility
Projects
- 2 Active
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MADNESS: Centre of Excellence in Materials-driven solutions for combatting antimicrobial resistance
Rosenholm, J. (Principal Investigator), Porres Paltor, I. (Co-Principal Investigator), Bansal, K. (Coordinator), Lafond, S. (Co-Principal Investigator), Uppstu, P. (Co-Principal Investigator), Viitala, T. (Co-Principal Investigator), Wang, X. (Co-Principal Investigator), Wilen, C.-E. (Co-Principal Investigator), Xu, C. (Co-Principal Investigator), Zhang, H. (Co-Principal Investigator), Lu, Z. (Co-Investigator), Verma, J. (Co-Investigator), Kumar, V. (Co-Investigator), Frejborg, F. (Co-Investigator), Wang, S. (Co-Investigator), Ran, M. (Co-Investigator), Ma, X. (Co-Investigator), Yang, W. (Co-Investigator), Liang, S. (Co-Investigator), Zhang, Y. (Co-Investigator), Fan, L. (Co-Investigator), Chen, Y. (Co-Investigator), Wang, L. (Co-Investigator), Zhuang, P. (Co-Investigator), Rajan Prakash, D. (Co-Investigator), Howaili, F. (Co-Investigator), Gulshan, R. (Co-Investigator), Yadav, D. (Co-Investigator), Pathak, C. (Co-Investigator), Mustafa, R. (Co-Investigator), Rostami, L. (Co-Investigator), Jafari Dargahlou, M. (Co-Investigator), Nygård, A. (Co-Investigator) & Manasut, P. (Co-Investigator)
01/01/24 → 31/12/28
Project: Foundation
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PII: Printed Intelligence Infrastructure
Toivakka, M. (Principal Investigator), Xu, C. (Co-Principal Investigator), Bobacka, J. (Co-Principal Investigator), Viitala, T. (Co-Principal Investigator), Rosenholm, J. (Co-Principal Investigator), Österbacka, R. (Co-Principal Investigator), Anttu, N. (Co-Principal Investigator), Huynh, T. P. (Co-Principal Investigator), Peltonen, J. (Co-Principal Investigator), Wang, X. (Co-Principal Investigator), Zhang, H. (Co-Principal Investigator) & Wilen, C.-E. (Co-Principal Investigator)
01/01/24 → 31/12/28
Project: Research Council of Finland/Other Research Councils